Diffusion Probabilistic Model Based Accurate and High-Degree-of-Freedom Metasurface Inverse Design

Conventional meta-atom designs rely heavily on researchers' prior knowledge and trial-and-error searches using full-wave simulations, resulting in time-consuming and inefficient processes. Inverse design methods based on optimization algorithms, such as evolutionary algorithms, and topological optimizations, have been introduced to design metamaterials. However, none of these algorithms are general enough to fulfill multi-objective tasks. Recently, deep learning methods represented by Generative Adversarial Networks (GANs) have been applied to inverse design of metamaterials, which can directly generate high-degree-of-freedom meta-atoms based on S-parameter requirements. However, the adversarial training process of GANs makes the network unstable and results in high modeling costs. This paper proposes a novel metamaterial inverse design method based on the diffusion probability theory. By learning the Markov process that transforms the original structure into a Gaussian distribution, the proposed method can gradually remove the noise starting from the Gaussian distribution and generate new high-degree-of-freedom meta-atoms that meet S-parameter conditions, which avoids the model instability introduced by the adversarial training process of GANs and ensures more accurate and high-quality generation results. Experiments have proven that our method is superior to representative methods of GANs in terms of model convergence speed, generation accuracy, and quality

Ada-DQA: Adaptive Diverse Quality-aware Feature Acquisition for Video Quality Assessment

Video quality assessment (VQA) has attracted growing attention in recent years. While the great expense of annotating large-scale VQA datasets has become the main obstacle for current deep-learning methods. To surmount the constraint of insufficient training data, in this paper, we first consider the complete range of video distribution diversity (\ie content, distortion, motion) and employ diverse pretrained models (\eg architecture, pretext task, pre-training dataset) to benefit quality representation. An Adaptive Diverse Quality-aware feature Acquisition (Ada-DQA) framework is proposed to capture desired quality-related features generated by these frozen pretrained models. By leveraging the Quality-aware Acquisition Module (QAM), the framework is able to extract more essential and relevant features to represent quality. Finally, the learned quality representation is utilized as supplementary supervisory information, along with the supervision of the labeled quality score, to guide the training of a relatively lightweight VQA model in a knowledge distillation manner, which largely reduces the computational cost during inference. Experimental results on three mainstream no-reference VQA benchmarks clearly show the superior performance of Ada-DQA in comparison with current state-of-the-art approaches without using extra training data of VQA.Comment: 10 pages, 5 figures, to appear in ACM MM 202

Multifunctions of CRIF1 in cancers and mitochondrial dysfunction

Sustaining proliferative signaling and enabling replicative immortality are two important hallmarks of cancer. The complex of cyclin-dependent kinase (CDK) and its cyclin plays a decisive role in the transformation of the cell cycle and is also critical in the initiation and progression of cancer. CRIF1, a multifunctional factor, plays a pivotal role in a series of cell biological progresses such as cell cycle, cell proliferation, and energy metabolism. CRIF1 is best known as a negative regulator of the cell cycle, on account of directly binding to Gadd45 family proteins or CDK2. In addition, CRIF1 acts as a regulator of several transcription factors such as Nur77 and STAT3 and partly determines the proliferation of cancer cells. Many studies showed that the expression of CRIF1 is significantly altered in cancers and potentially regarded as a tumor suppressor. This suggests that targeting CRIF1 would enhance the selectivity and sensitivity of cancer treatment. Moreover, CRIF1 might be an indispensable part of mitoribosome and is involved in the regulation of OXPHOS capacity. Further, CRIF1 is thought to be a novel target for the underlying mechanism of diseases with mitochondrial dysfunctions. In summary, this review would conclude the latest aspects of studies about CRIF1 in cancers and mitochondria-related diseases, shed new light on targeted therapy, and provide a more comprehensive holistic view

Highly-stable, flexible delivery of microjoule-level ultrafast pulses in vacuumized anti-resonant hollow-core fibers for active synchronization

We demonstrate the stable and flexible light delivery of multi-{\mu}J, sub-200-fs pulses over a ~10-m-long vacuumized anti-resonant hollow-core fiber (AR-HCF), which was successfully used for high-performance pulse synchronization. Compared with the pulse train launched into the AR-HCF, the transmitted pulse train out of the fiber exhibits excellent stabilities in pulse power and spectrum, with pointing stability largely improved. The walk-off between the fiber-delivery and the other free-space-propagation pulse trains, in an open loop, was measured to be <6 fs root-mean-square (RMS) over 90 minutes, corresponding to a relative optical-path variation of <2x10-7. This walk-off can be further suppressed to ~2 fs RMS simply using an active control loop, highlighting the great application potentials of this AR-HCF set-up in large-scale laser and accelerator facilities

NAT10 Maintains OGA mRNA Stability Through ac4C Modification in Regulating Oocyte Maturation

In vitro maturation (IVM) refers to the process of developing immature oocytes into the mature in vitro under the microenvironment analogous to follicle fluid. It is an important technique for patients with polycystic ovary syndrome and, especially, those young patients with the need of fertility preservation. However, as the mechanisms of oocyte maturation have not been fully understood yet, the cultivation efficiency of IVM is not satisfactory. It was confirmed in our previous study that oocyte maturation was impaired after N-acetyltransferase 10 (NAT10) knockdown (KD). In the present study, we further explored the transcriptome alteration of NAT10-depleted oocytes and found that O-GlcNAcase(OGA) was an important target gene for NAT10-mediated ac4C modification in oocyte maturation. NAT10 might regulate OGA stability and expression by suppressing its degradation. To find out whether the influence of NAT10-mediated ac4C on oocyte maturation was mediated by OGA, we further explored the role of OGA in IVM. After knocking down OGA of oocytes, oocyte maturation was inhibited. In addition, as oocytes matured, OGA expression increased and, conversely, O-linked N-acetylglucosamine (O-GlcNAc) level decreased. On the basis of NAT10 KD transcriptome and OGA KD transcriptome data, NAT10-mediated ac4C modification of OGA might play a role through G protein–coupled receptors, molecular transduction, nucleosome DNA binding, and other mechanisms in oocyte maturation. Rsph6a, Gm7788, Gm41780, Trpc7, Gm29036, and Gm47144 were potential downstream genes. In conclusion, NAT10 maintained the stability of OGA transcript by ac4C modification on it, thus positively regulating IVM. Moreover, our study revealed the regulation mechanisms of oocytes maturation and provided reference for improving IVM outcomes. At the same time, the interaction between mRNA ac4C modification and protein O-GlcNAc modification was found for the first time, which enriched the regulation network of oocyte maturation

Comparison of staged-stent and stent-assisted coiling technique for ruptured saccular wide-necked intracranial aneurysms: Safety and efficacy based on a propensity score-matched cohort study

BackgroundApplication of stent-assisted coiling and FD in acute phase of ruptured wide-necked aneurysms is relatively contraindicated due to the potential risk of ischemic and hemorrhagic complications. Scheduled stenting after initial coiling has emerged as an alternative paradigm for ruptured wide-necked aneurysms. The objective of this study is to evaluate the safety and efficacy of a strategy of staged stent-assisted coiling in acutely ruptured saccular wide-necked intracranial aneurysms compared with conventional early stent-assisted coiling strategy via propensity score matching in a high-volume center.MethodsA retrospective review of patients with acutely ruptured saccular wide-necked intracranial aneurysms who underwent staged stent-assisted coiling or conventional stent-assisted coiling from November 2014 to November 2019 was performed. Perioperative procedure-related complications and clinical and angiographic follow-up outcomes were compared.ResultsA total of 69 patients with staged stent-assisted coiling and 138 patients with conventional stent-assisted coiling were enrolled after 1:2 propensity score matching. The median interval time between previous coiling and later stenting was 4.0 weeks (range 3.5–7.5 weeks). No rebleeding occurred during the intervals. The rate of immediate complete occlusion was lower with initial coiling before scheduled stenting than with conventional stent-assisted coiling (21.7 vs. 60.9%), whereas comparable results were observed at follow-up (82.5 vs. 72.9%; p = 0.357). The clinical follow-up outcomes, overall procedure-related complications and procedure-related mortality between the two groups demonstrated no significant differences (P = 0.232, P = 0.089, P = 0.537, respectively). Multivariate analysis showed that modified Fisher grades (OR = 2.120, P = 0.041) were independent predictors for overall procedure-related complications and no significant predictors for hemorrhagic and ischemic complications.ConclusionsStaged stent-assisted coiling is a safe and effective treatment strategy for acutely ruptured saccular wide-necked intracranial aneurysms, with comparable complete occlusion rates, recurrence rates at follow-up and overall procedure-related complication rates compared with conventional stent-assisted coiling strategy. Staged stent-assisted coiling could be an alternative treatment option for selected ruptured intracranial aneurysms in the future

A Better Anti-Diabetic Recombinant Human Fibroblast Growth Factor 21 (rhFGF21) Modified with Polyethylene Glycol

As one of fibroblast growth factor (FGF) family members, FGF21 has been extensively investigated for its potential as a drug candidate to combat metabolic diseases. In the present study, recombinant human FGF21 (rhFGF21) was modified with polyethylene glycol (PEGylation) in order to increase its in vivo biostabilities and therapeutic potency. At N-terminal residue rhFGF21 was site-selectively PEGylated with mPEG20 kDa-butyraldehyde. The PEGylated rhFGF21 was purified to near homogeneity by Q Sepharose anion-exchange chromatography. The general structural and biochemical features as well as anti-diabetic effects of PEGylated rhFGF21 in a type 2 diabetic rat model were evaluated. By N-terminal sequencing and MALDI-TOF mass spectrometry, we confirmed that PEG molecule was conjugated only to the N-terminus of rhFGF21. The mono-PEGylated rhFGF21 retained the secondary structure, consistent with the native rhFGF21, but its biostabilities, including the resistance to physiological temperature and trypsinization, were significantly enhanced. The in vivo immunogenicity of PEGylated rhFGF21 was significantly decreased, and in vivo half-life time was significantly elongated. Compared to the native form, the PEGylated rhFGF21 had a similar capacity of stimulating glucose uptake in 3T3-L1 cells in vitro, but afforded a significantly long effect on reducing blood glucose and triglyceride levels in the type 2 diabetic animals. These results suggest that the PEGylated rhFGF21 is a better and more effective anti-diabetic drug candidate than the native rhFGF21 currently available. Therefore, the PEGylated rhFGF21 may be potentially applied in clinics to improve the metabolic syndrome for type 2 diabetic patients

A Novel Solid-Phase Site-Specific PEGylation Enhances the In Vitro and In Vivo Biostabilty of Recombinant Human Keratinocyte Growth Factor 1

Keratinocyte growth factor 1 (KGF-1) has proven useful in the treatment of pathologies associated with dermal adnexae, liver, lung, and the gastrointestinal tract diseases. However, poor stability and short plasma half-life of the protein have restricted its therapeutic applications. While it is possible to improve the stability and extend the circulating half-life of recombinant human KGF-1 (rhKGF-1) using solution-phase PEGylation, such preparations have heterogeneous structures and often low specific activities due to multiple and/or uncontrolled PEGylation. In the present study, a novel solid-phase PEGylation strategy was employed to produce homogenous mono-PEGylated rhKGF-1. RhKGF-1 protein was immobilized on a Heparin-Sepharose column and then a site-selective PEGylation reaction was carried out by a reductive alkylation at the N-terminal amino acid of the protein. The mono-PEGylated rhKGF-1, which accounted for over 40% of the total rhKGF-1 used in the PEGylation reaction, was purified to homogeneity by SP Sepharose ion-exchange chromatography. Our biophysical and biochemical studies demonstrated that the solid-phase PEGylation significantly enhanced the in vitro and in vivo biostability without affecting the over all structure of the protein. Furthermore, pharmacokinetic analysis showed that modified rhKGF-1 had considerably longer plasma half-life than its intact counterpart. Our cell-based analysis showed that, similar to rhKGF-1, PEGylated rhKGF-1 induced proliferation in NIH 3T3 cells through the activation of MAPK/Erk pathway. Notably, PEGylated rhKGF-1 exhibited a greater hepatoprotection against CCl4-induced injury in rats compared to rhKGF-1